Physician Perspective and Challenges Ordering/Interpreting Laboratory Tests Related to the Opioid Crisis in America.

ABSTRACT: The opioid crisis is a profound public health crisis in the United States. It has significantly increased morbidity and mortality in our nation. There are many contributing factors to the opioid crisis, including a strong national and international interest to treat pain as effectively as possible. To combat this crisis, numerous strategies have been implemented over the past few years at the legislative, health system, and patient levels. As a result of these efforts, for the first time since 1999, drug overdose deaths in the United States decreased from 2017 to 2018, when deaths involving all opioids, prescription opioids, and heroin decreased by 2%, 13.5%, and 4.1%, respectively. To continue to curb the opioid crisis, it is imperative to optimize pain control through multidisciplinary and multimodal approaches and to adhere to opioid prescribing guidelines from regulatory and professional organizations to minimize risks for opioid misuse and abuse. Urine drug testing is an important means to assist with opioid monitoring and safe opioid prescribing. There are challenges when ordering urine drug tests, collecting specimens, and interpreting test results. Inaccurate interpretations of laboratory results can have significantly negative impacts on patients care and life. There is a critical need for prescriber education by laboratory experts in the use of drug testing and interpretation of results. To interpret test results correctly and make safe prescribing decisions, it is very important for prescribers/providers to consult clinical toxicologists, laboratory directors, and reporting staff. This interaction is vital and provides excellence of care for patients. This review aims to provide information concerning the opioid crisis in the United States and summarizes the challenges ordering and interpreting opioid-related laboratory testing as well as pertinent guidelines and recommendations.

Pain management in the 21st century: utilization of pharmacogenomics and therapeutic drug monitoring.

INTRODUCTION: Anesthesiologists and pain management physicians recognize that the key to clinical success is the ability to effectively control pain and related symptoms in patients without causing excess side effects from prescribed medications. The use of opioids for pain management is broadly accepted by regulatory bodies, professional organizations (i.e., the WHO) and physicians, as is the wide range of patient responses to these medications. Pharmacogenomics and therapeutic drug monitoring are two underutilized tools which can be implemented to best predict and monitor which opioid and dose may be the most appropriate for an individual patient. AREAS COVERED: This review summarizes and discusses evidence for the use of genetic analysis to guide the selection and modification of opioid therapy along with the use of therapeutic drug monitoring to objectively check therapeutic outcomes and compliance. The reader will gain an understanding of the most notable genetic polymorphisms that can affect a patient's response to commonly prescribed opioids, along with the clinical benefits of genotyping and performing therapeutic drug monitoring. EXPERT OPINION: In the end, the authors strongly believe that objective tools such as pharmacogenomics and therapeutic drug monitoring provide added benefit (minimizing adverse effects, while maximizing efficacy) and will ultimately advance the practice of pain management by incorporating these tools into the standard of care.

Pharmacogenomic considerations in the opioid management of pain.

Physicians continue to struggle with the clinical management of pain, in part because of the large interindividual variability in the efficacy, occurrence of side effects and undesired severe adverse drug reactions from the prescribed analgesics. Pharmacogenomics, the study of how an individual's genetic inheritance affects the body's response to medications, has an important role and can explain some of this interindividual variability. Genetic identification of known variant alleles that affect the pharmacokinetics or pharmacodynamics of medications used for pain management can enable physicians to select the appropriate analgesic drug and dosing regimen for an individual patient, instead of empirical selection and dosing escalation. In this article, clinically relevant pharmacogenomic targets for the management of opioid pain, including efflux transporters, proteins that metabolize drugs, enzymes that regulate the neurotransmitters that modulate pain, and opioid receptors, will be reviewed.

Utilization of pharmacogenomics and therapeutic drug monitoring for opioid pain management.

AIMS: The use of medication in pain management currently involves empirical adjustment based on observed clinical outcome and the presence of adverse drug reactions. In this study, pharmacogenomics and therapeutic drug monitoring were used to evaluate the clinical effectiveness of genotyping chronic pain patients on analgesic therapy. It was hypothesized that patients who have inherited polymorphisms in CYP2D6 that make them poor or intermediate metabolizers of opioid medications would have higher steady-state concentrations of those opioids and may be more likely to experience adverse drug reactions. MATERIALS & METHODS: In an attempt to investigate the relationship between the polymorphic enzymes, steady-state drug concentrations, therapeutic effects and side effects, 61 patients were clinically evaluated and genotyped, and drug concentrations were measured and outcomes analyzed. Samples were collected and DNA extracted from whole blood using a Puregene DNA isolation kit. CYP2D6 genotyping (*3, *4, *5, *6, *7, *8 and gene duplication) were carried out using Pyrosequencing. Steady-state plasma concentrations of methadone, oxycodone, hydrocodone and tramadol were determined by HPLC tandem mass spectrometry. RESULTS: The results demonstrated the prevalence of CYP2D6 polymorphisms in the population undergoing pain management was not statistically different from the general population. The majority of the pain patients (54%) were extensive metabolizers; 41% were intermediate metabolizers and 5% poor metabolizers. Poor metabolizers in general tended to have the highest steady-state drug concentrations compared with extensive metabolizers (poor metabolizers > intermediate metabolizers > extensive metabolizers) although this wasn't statistically significant. Also, a relationship between oxycodone steady-state drug concentrations and pain relief was found. A total of 80% of patients reporting adverse drug reactions also had impaired CYP2D6 metabolism. The remaining 20% with adverse drug reactions had other cofactors (i.e., drug-drug interactions) that could explain the toxicity. CONCLUSION: These results suggest that patient care may be improved by genotyping and following therapeutic drug concentrations. Benefits include increased efficiency in proper drug selection, dose optimization and minimization of adverse drug reactions to improve patient outcome and safety. In addition, this study clearly demonstrated a relationship between oxycodone steady-state drug concentrations and pain relief. Future large-scale prospective studies are needed to confirm the clinical value of using genetic information to guide pain management therapy.